Departments of VIP Unit, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China.
Departments of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China.
BMC Med Genomics. 2021 Feb 1;14(1):35. doi: 10.1186/s12920-021-00877-3.
Type 1 diabetes (T1D, named insulin-dependent diabetes) has a relatively rapid onset and significantly decreases life expectancy. This study is conducted to reveal the long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA regulatory axises implicated in T1D.
The gene expression profile under GSE55100 (GPL570 and GPL8786 datasets; including 12 T1D samples and 10 normal samples for each dataset) was extracted from Gene Expression Omnibus database. Using limma package, the differentially expressed mRNAs (DE-mRNAs), miRNAs (DE-miRNAs), and lncRNAs (DE-lncRNAs) between T1D and normal samples were analyzed. For the DE-mRNAs, the functional terms were enriched by DAVID tool, and the significant pathways were enriched using gene set enrichment analysis. The interactions among DE-lncRNAs, DE-miRNAs and DE-mRNAs were predicted using mirwalk and starbase. The lncRNA-miRNA-mRNA interaction network analysis was visualized by Cytoscape. The key genes in the interaction network were verified by quantitatively real-time PCR.
In comparison to normal samples, 236 DE-mRNAs, 184 DE-lncRNAs, and 45 DE-miRNAs in T1D samples were identified. For the 236 DE-mRNAs, 16 Gene Ontology (GO)_biological process (BP) terms, four GO_cellular component (CC) terms, and 57 significant pathways were enriched. A network involving 36 DE-mRNAs, 8 DE- lncRNAs, and 15 DE-miRNAs was built, such as TRG-AS1-miR-23b/miR-423-PPM1L and GAS5-miR-320a/miR-23b/miR-423-SERPINA1 regulatory axises. Quantitatively real-time PCR successfully validated the expression levels of TRG-AS1- miR-23b -PPM1L and GAS5-miR-320a- SERPINA1.
TRG-AS1-miR-23b-PPM1L and GAS5-miR-320a-SERPINA1 regulatory axises might impact the pathogenesis of T1D.
1 型糖尿病（T1D，也称胰岛素依赖型糖尿病）发病迅速，显著缩短预期寿命。本研究旨在揭示与 T1D 相关的长链非编码 RNA（lncRNA）-微小 RNA（miRNA）-mRNA 调控轴。
从基因表达综合数据库中提取基因表达谱数据集 GSE55100（GPL570 和 GPL8786 数据集；每个数据集包括 12 例 T1D 样本和 10 例正常样本）。使用 limma 包分析 T1D 与正常样本间差异表达的信使 RNA（DE-mRNA）、miRNA（DE-miRNA）和 lncRNA（DE-lncRNA）。针对 DE-mRNA，采用 DAVID 工具进行功能术语富集，采用基因集富集分析进行显著通路富集。使用 mirwalk 和 starbase 预测 DE-lncRNA、DE-miRNA 与 DE-mRNA 间的相互作用。通过 Cytoscape 可视化 lncRNA-miRNA-mRNA 相互作用网络分析。通过定量实时 PCR 验证互作网络中的关键基因。
与正常样本相比，T1D 样本中发现 236 个 DE-mRNA、184 个 DE-lncRNA 和 45 个 DE-miRNA。针对 236 个 DE-mRNA，进行了 16 个基因本体论（GO）生物过程（BP）术语、4 个 GO 细胞成分（CC）术语和 57 个显著通路的富集分析。构建了一个包含 36 个 DE-mRNA、8 个 DE-lncRNA 和 15 个 DE-miRNA 的网络，如 TRG-AS1-miR-23b/miR-423-PPM1L 和 GAS5-miR-320a/miR-23b/miR-423-SERPINA1 调控轴。定量实时 PCR 成功验证了 TRG-AS1-miR-23b-PPM1L 和 GAS5-miR-320a-SERPINA1 的表达水平。
TRG-AS1-miR-23b-PPM1L 和 GAS5-miR-320a-SERPINA1 调控轴可能影响 T1D 的发病机制。
